Chronic cochlear implantation with and without electric stimulation in a mouse model induces robust cochlear influx of CX3CR1+/GFP macrophages

BACKGROUND: Cochlear implantation is an effective auditory rehabilitation strategy for those with profound hearing loss, including those with residual low frequency hearing through use of hybrid cochlear implantation techniques. Post-mortem studies demonstrate the nearly ubiquitous presence of intracochlear fibrosis and neo-ossification following cochlear implantation. Current evidence suggests post-implantation intracochlear fibrosis is associated with delayed loss of residual acoustic hearing in hybrid cochlear implant (CI) recipients and may also negatively influence outcomes in traditional CI recipients. This study examined the contributions of surgical trauma, foreign body response and electric stimulation to intracochlear fibrosis and the innate immune response to cochlear implantation and the hierarchy of these contributions. METHODS: Normal hearing CX3CR1 RESULTS: A ST peri-implant cellular infiltrate and fibrosis occurred exclusively in the chronically implanted groups starting on day 7 with a concurrent infiltration of CX3CR1+ macrophages not seen in the other groups. CX3CR1+ macrophage infiltration was seen in the LW and RC in all experimental groups within the first week, being most prominent in the 3 chronically implanted groups during the second and third week. CONCLUSIONS: The cochlear immune response was most prominent in the presence of chronic cochlear implantation, regardless of electric stimulation level. Further, the development of intracochlear ST fibrosis was dependent on the presence of the indwelling CI foreign body. An innate immune response was evoked by surgical trauma alone (sham and acute CI groups) to a lesser degree. These data suggest that cochlear inflammation and intrascalar fibrosis after cochlear implantation are largely dependent on the presence of a chronic indwelling foreign body and are not critically dependent on electrical stimulation. Also, these data support a role for surgical trauma in inciting the initial innate immune response

Contribution of macrophages to neural survival and intracochlear tissue remodeling responses following cochlear implantation

BACKGROUND: Cochlear implants (CIs) restore hearing to deafened patients. The foreign body response (FBR) following cochlear implantation (post-CI) comprises an infiltration of macrophages, other immune and non-immune cells, and fibrosis into the scala tympani, a space that is normally devoid of cells. This FBR is associated with negative effects on CI outcomes including increased electrode impedances and loss of residual acoustic hearing. This study investigates the extent to which macrophage depletion by an orally administered CSF-1R specific kinase (c-FMS) inhibitor, PLX-5622, modulates the tissue response to CI and neural health. MAIN TEXT: 10- to 12-week-old CX3CR1 + /GFP Thy1 + /YFP mice on C57BL/6J/B6 background was fed chow containing 1200 mg/kg PLX5622 or control chow for the duration of the study. 7 days after starting the diet, 3-channel cochlear implants were implanted in the ear via the round window. Serial impedance and neural response telemetry (NRT) measurements were acquired throughout the study. Electric stimulation began 7 days post-CI until 28 days post-CI for 5 h/day, 5 days/week, with programming guided by NRT and behavioral responses. Cochleae harvested at 10, 28 or 56 days post-CI were cryosectioned and labeled with an antibody against α-smooth muscle actin (α-SMA) to identify myofibroblasts and quantify the fibrotic response. Using IMARIS image analysis software, the outlines of scala tympani, Rosenthal canal, modiolus, and lateral wall for each turn were traced manually to measure region volume. The density of nuclei, CX3CR1 + macrophages, Thy1 + spiral ganglion neuron (SGN) numbers, and the ratio of the α-SMA + volume/scala tympani volume were calculated. Cochlear implantation in control diet subjects caused infiltration of cells, including macrophages, into the cochlea. Fibrosis was evident in the scala tympani adjacent to the electrode array. Mice fed PLX5622 chow showed reduced macrophage infiltration throughout the implanted cochleae across all time points. However, scala tympani fibrosis was not reduced relative to control diet subjects. Further, mice treated with PLX5622 showed increased electrode impedances compared to controls. Finally, treatment with PLX5622 decreased SGN survival in implanted and contralateral cochleae. CONCLUSION: The data suggest that macrophages play an important role in modulating the intracochlear tissue response following CI and neural survival

Supermassive Black Holes in Galactic Nuclei: Past, Present and Future Research

This review discusses the current status of supermassive black hole research, as seen from a purely observational standpoint. Since the early '90s, rapid technological advances, most notably the launch of the Hubble Space Telescope, the commissioning of the VLBA and improvements in near-infrared speckle imaging techniques, have not only given us incontrovertible proof of the existence of supermassive black holes, but have unveiled fundamental connections between the mass of the central singularity and the global properties of the host galaxy. It is thanks to these observations that we are now, for the first time, in a position to understand the origin, evolution and cosmic relevance of these fascinating objects.Comment: Invited Review, 114 pages. Because of space requirements, this version contains low resolution figures. The full resolution version can be downloaded from http://www.physics.rutgers.edu/~lff/publications.htm

Climatic impacts of land-use change due to crop yield increases and a universal carbon tax from a scenario model*

Future land cover will have a significant impact on climate and is strongly influenced by the extent of agricultural land use. Differing assumptions of crop yield increase and carbon pricing mitigation strategies affect projected expansion of agricultural land in future scenarios. In the representative concentration pathway 4.5 (RCP4.5) from phase 5 of the Coupled Model Intercomparison Project (CMIP5), the carbon effects of these land cover changes are included, although the biogeophysical effects are not. The afforestation in RCP4.5 has important biogeophysical impacts on climate, in addition to the land carbon changes, which are directly related to the assumption of crop yield increase and the universal carbon tax. To investigate the biogeophysical climatic impact of combinations of agricultural crop yield increases and carbon pricing mitigation, five scenarios of land-use change based on RCP4.5 are used as inputs to an earth system model [Hadley Centre Global Environment Model, version 2-Earth System (HadGEM2-ES)]. In the scenario with the greatest increase in agricultural land (as a result of no increase in crop yield and no climate mitigation) there is a significant -0.49 K worldwide cooling by 2100 compared to a control scenario with no land-use change. Regional cooling is up to -2.2 K annually in northeastern Asia. Including carbon feedbacks from the land-use change gives a small global cooling of -0.067 K. This work shows that there are significant impacts from biogeophysical land-use changes caused by assumptions of crop yield and carbon mitigation, which mean that land carbon is not the whole story. It also elucidates the potential conflict between cooling from biogeophysical climate effects of land-use change and wider environmental aims

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Roadmap on printable electronic materials for next-generation sensors

The dissemination of sensors is key to realizing a sustainable, ‘intelligent’ world, where everyday objects and environments are equipped with sensing capabilities to advance the sustainability and quality of our lives—e.g., via smart homes, smart cities, smart healthcare, smart logistics, Industry 4.0, and precision agriculture. The realization of the full potential of these applications critically depends on the availability of easy-to-make, low-cost sensor technologies. Sensors based on printable electronic materials offer the ideal platform: they can be fabricated through simple methods (e.g., printing and coating) and are compatible with high-throughput roll-to-roll processing. Moreover, printable electronic materials often allow the fabrication of sensors on flexible/stretchable/biodegradable substrates, thereby enabling the deployment of sensors in unconventional settings. Fulfilling the promise of printable electronic materials for sensing will require materials and device innovations to enhance their ability to transduce external stimuli—light, ionizing radiation, pressure, strain, force, temperature, gas, vapours, humidity, and other chemical and biological analytes. This Roadmap brings together the viewpoints of experts in various printable sensing materials—and devices thereof—to provide insights into the status and outlook of the field. Alongside recent materials and device innovations, the roadmap discusses the key outstanding challenges pertaining to each printable sensing technology. Finally, the Roadmap points to promising directions to overcome these challenges and thus enable ubiquitous sensing for a sustainable, ‘intelligent’ world

Stimulated 3D X-ray MS5-20 part 1/2

Stimulated 3D X-ray MS5-20 part 1/2 raw image, split with HJSpli